Ether preservation



United States Patent Ofiice 2,720,544 Patented Oct. 11, 1955 ETHERPRESERVATION Edward Mallinckrodt, Jr., St. Louis, and Archie E. Ruehle,Kirkwood, Mo., assignors to Maliinckrodt Chemical Works, St. Louis, Mo.,a corporation of Missouri No Drawing. Application July 19, 1954, SerialNo. 444,391

11 Claims. (Cl. 260-6115) This invention relates to ether preservation,and more particularly to the preservation of ether by means of certaindithizone preservative compounds.

Briefly, this invention relates to a composition com prising ether and apreservative compound selected from the group consisting of dithizone,cupric dithizonate, lead dithizonate and stannous dithizonate. Theinvention also relates to the method of preserving ether which comprisesdissolving therein a preservative compound selected from the above-notedgroup.

Among the objects of the invention may be noted the provision ofimproved means of preserving ether against decomposition; the provisionof such means which are efiective in minute quantities to preserveether; and the provision of means of the character described whichpreserve ether for relatively long periods of time. Other objects andfeatures will be in part apparent and in part pointed out hereinafter.

The inventionaccordingly comprises the products and methods hereinafterdescribed, the scope of the invention being indicated in the followingclaims.

Diethyl ether in untreated tin cans, within a short time following itsmanufacture, may acquire sufficient decomposition products to make itfail to pass the United States Pharmacopoeias rigorous requirements forether intended for anesthesia. In recognition of these properties ofether, the Pharmacopoeia requires that ether for anesthesia be packed intight containers of not more than 3 kg. capacity and that it be usedwithin twenty-four hours after removal from the original container.Peroxide and aldehyde impurities are particularly objectionable inanesthetic ether, and indeed are limited to the merest traces by thespecification of the United States Pharmacopoeia. Once started, theformation of peroxides may increase through auto-oxidation. Heat, light,air and catalytically active surfaces inside the container influence theformation of ether peroxides. The eifects of these factors on theformation of peroxide impurities may be considerably minimized byforming on the cans inner surface an adherent layer of tin oxide or acoating of metallic copper. Such expedients, however, are not entirelysatisfactory. The best results have been obtained with a containerhaving a copper-tin oxide coating on the inside surface, as describedand claimed in our U. S. Patent No. 2,587,744, issued March 4, 1952.Another expedient which has been employed is the addition of apreservative to the ether which prevents or inhibits peroxide formation.Hydroquinone and diphenylamine are well-known preservatives; but thesecompounds possess only limited usefulness.

In accordance with the present invention, dithizone(diphenylthiocarbazone) and certain dithizonate metal organic complexeshave been found which exhibit an improved preserving action on ether.When dissolved in ether in minute amounts, they are effective inpreventing, inhibiting or delaying the formation of peroxides, therebyprolonging the keeping time of ether following manufacture. The use ofthese preservative compounds in conjunction with treated or coatedcontainers, such as mentioned above, is particularly advantageous andconsiderably increases the stability of ether in storage. In addition todithizone, the particular dithizonate salts which have been foundeffective in preserving ether are the cupric, lead and stannous salts.

These dithizone preservative compounds of this invention are moreeffective than hydroquinone to increase the keeping time of ether evenat concentrations onetenth to one-hundredth that of hydroquinone. Allthe compounds of the present invention exhibit improved preservingaction at a concentration of only 10- molar or less when compared withhydroquinone at ten times this concentration (IO- molar). Furthermore,when employed in conjunction with treated containers having an interioradherent coating of copper-tin oxide or lacquer varnish, still smallerconcentrations of these preservative compounds are efiective.

The following examples illustrate the invention.

Example 1 The preservative action of these compounds upon ether wasdemonstrated by an accelerated aging test of the compositions of thepresent invention under conditions which favor the rapid spoilage ofether, i. e., contact with a polished tin surface and shaking it at atemperature of F. for sixteen hours. The preservatives to be tested weredissolved in freshly distilled anhydrous (absolute) ether, initiallycontaining less than 0.05 p. p. m. peroxide and less than 2-3 p. p. m.aldehyde, and made up to the desired concentration. By this test, therelative effectiveness of various preservatives and other methods ofpreserving ether can be determined.

At the end of the sixteen-hour test period the ether was tested for theamount of peroxide and aldehyde it contained. If the sample was found tocontain more than 0.2 part per million peroxide (the U. S. P. limitcorresponds to about 0.5 p. p. m.) or over 3 p. p. m. aldehyde asacetaldehyde (the U. S. P. limit corresponds to slightly over 13 p. p.In.) it was considered to have failed in the test. In carrying out thetests, the preservative is added to 18 ml. of freshly distilled ether ina tin vessel half full, the inner surfaces of which have been mildlyabraded to remove surface film or tarnish, and the vessels shaken 16hours at a temperature of 100 F. The well-known ammoniumthiocyanate-ferrous sulphate reaction was used with a set of standardcolors to determine the peroxides, and Nesslers reagent with colorstandards was used to estimate the aldehyde.

In the case of hydroquinone, it was found that, at a concentration of10* molar (ll mg./l.), twenty out of twenty-one samples passed theaccelerated aging test with respect to peroxide, whereas, at aconcentration of 10- molar 1.1 mg./l.) only ten out of fifty-two samplespassed. The color test for aldehyde could not be read at 10* molarbecause hydroquinone at this concentration interferes with the test; butat a concentration of 10* molar nearly half of the samples failed. Ineach series of tests, samples of ether containing no preservatives wereincluded to be certain that the conditions were such that untreatedether would spoil during the sixteenhour test period.

Three samples of ether containing diphenylamine at a concentration of10" molar (1.7 mg./l.) and three samples containing the same compound ata concentration of 10 molar (0.17 rug/l.) were also prepared and tested.All six samples failed both the peroxide and aldehyde tests.

Three samples of ether containing dithizone at a concentration of 10*molar (2.56 mg./l.), nine at 10 molar (0.256 mg./l.) and twelve at 10-molar 3 (0.0256 mg./l.) were tested by the above procedure. At the endof the accelerated aging test it was found that all samples at aconcentration of 10 and lO molar passed both the aldehyde and peroxidetests, while at a concentration of molar six samples passed the aldehydeand peroxide tests.

Example 2 Example 1 was repeated except that three samples of ethercontaining cupric dithizonate at a concentration of 5X10 molar (2.86mg./l.) and six samples at a concentration of 5x10 molar (0.286 mg./l.)Were employed. At both these concentrations, all samples passed both thealdehyde and peroxide tests.

Example 3 Example 1 was repeated except that three samples of ethercontaining lead dithizonate at a concentration of 5 10- molar (3.58mg./l.) were employed. All sam plcs passed both the aldehyde andperoxide tests.

Example 4 Example 1 was repeated except that three samples of ethercontaining stannous dithizonate at a concentration of 5X10 molar (3.13mg./l.) were employed. All samples passed both the aldehyde and peroxidetests.

Thus, the ether preservatives of the present invention when testedaccording to the accelerated aging tests are many times (e. g., ten toone hundred) more efiective in preserving ether than hydroquinone asdetermined by standards higher than those required by the U. S.Pharmacopoeia. Moreover, when the preservative compounds of thisinvention are employed in conjunction with treated containers such as acopper-tin oxide coated can, for example, concentrations even smallerthan those used in the foregoing examples are efiective to preserveether for extended periods of time.

In view of the 'above, it will be seen that the several objects of theinvention are achieved and other advantageous results attained.

4. A composition comprising ether and lead dithizonate.

5. A composition comprising ether and stannous dithizonate.

6. The method of preserving ether which comprises dissolving therein acompound selected from the group consisting of dithizone, cupricdithizonate, lead dithizonate and stannous dithizonate.

7. The method of preservingether which comprises confining in anair-tight container ether having dissolved therein a compound selectedfrom the group consisting of dithizone, cupric dithizonate, leaddithizonate and stannous dithizonate.

8. The method of preserving ether which comprises confining in anair-tight container. ether having dissolved therein dithizone.

9. The method of preserving ether which comprises confining in anair-tight container ether having dissolved therein cupric dithizonate.

10. The method of preserving ether which comprises confining in anair-tight container ether having dissolved therein lead dithizonate.

11. The method of preserving ether which comprises confining in anair-tight container ether having dissolved therein stannous dithizonate.

No references cited.

1. A COMPOSITION COMPRISING ETHER AND A PRESEVATIVE COMPOUND SELECTEDFROM THE GROUP CONSISTING OF DITHIZONE, CUPRIC DITHIZONATE, LEADDITHIZONATE AND STANNOUS DITHIZONATE.